Is MTOR p.Ala690Val (c.2069C>T) pathogenic?

MTOR p.Ala690Val (c.2069C>T) is classified Conflicting classifications of pathogenicity in MTOR (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-12). AlphaMissense: likely pathogenic (0.7842); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with MTOR p.Ala690Val (c.2069C>T)?

MTOR p.Ala690Val (c.2069C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MTOR p.Ala690Val (c.2069C>T) in the general population?

MTOR p.Ala690Val (c.2069C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about MTOR p.Ala690Val (c.2069C>T)?

AlphaMissense predicts likely pathogenic (score 0.7842) — an in-silico prediction, not a clinical call.

MTOR p.Ala690Val

c.2069C>T · rs779998245 · VCV2144641

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7842 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7842	likely pathogenic
REVEL	0.314	indeterminate
SaProt	LLR -6.84	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 26 kb · p 2.5e-27 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000752% 11/1,461,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.00446%	22,441
South Asian	0.0022%	45,537
Admixed American	0.00167%	60,024
African / African-American	0.00133%	75,052
European (non-Finnish)	0.000339%	295,009

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MTOR
Protein: p.Ala690Val
Coding: c.2069C>T
MANE Select: NM_004958
dbSNP: rs779998245
Type: single nucleotide variant
Location: chr1:11237982 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 690: an α-helix

Full MTOR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTOR p.Ala690= Benign/Likely benign ★★ same residue
MTOR c.5365-5A>G Uncertain significance ★★ same condition
MTOR p.Ala352Ser Uncertain significance ★★ ⚠ same condition
MTOR p.Arg1818Cys Uncertain significance ★★ ⚠ same condition
MTOR p.Arg2060Gln Uncertain significance ★★ ⚠ same condition
MTOR p.Arg2110Gln Uncertain significance ★★ ⚠ same condition
MTOR p.Arg2217Gln Uncertain significance ★★ ⚠ same condition
MTOR p.Arg2445Gly Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mtor-p-ala690val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown